Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system, causing unpredictable and varying symptoms that differ from person to person. About 1 in 700 people in the United States is affected by the disease. Because MS often runs in families, it’s thought that there is a substantial genetic component to the disease.

But genetics aren’t the whole story. If one identical twin has MS, the chance that the other twin will also have the disease is increased by only 30%. Although this is more than the 5% increase in risk seen in non-identical twins, the fact that identical twins (who are theoretically completely the same at the DNA level) are not always concordant for MS has led researchers to assume that environmental factors of some sort must also play an important role. Everything from viral infections to vitamin D deficiency due to low sun exposure has been suggested.

But the true identical-ness of identical twins has been called into question in recent years. Research has shown that there may be subtle differences in their genomes. To test whether tiny changes—either in DNA sequence, gene expression, or chemical modifications to the genome—might play a role in determining why one twin gets MS while the other is spared, researchers from the University of California, San Francisco and the National Center for Genome Resources used a variety of methods to go over the genomes of three sets of MS-discordant identical twins in unprecedented detail.

No matter how the scientists looked at the twins’ genetics, nothing stood out to explain their differences in disease status. These results, published online today in the journal Nature, are strong evidence that when it comes to MS, identical twins might enter the world with the same risk, but their individual experiences and exposures determine whether each one will get the disease.

The data from just these three twin pairs gives researchers important information about the relative contributions of genetic and environmental factors in MS. But more work will be needed to replicate these results and to look even more closely at individual genomes. The study’s lead author Sergio Baranzini said in a press release that his team will be able to broaden their study and look at even more twin pairs thanks to steady reductions in the cost of genome sequencing.

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